42017-89-0

White to Off-White Solid

DPP4 inhibitor, antidiabetic

Fenofibric acid, the active metabolite of fenofibrate. Increases Apolipoprotein A-Iediated High-Density Lipoprotein Biogenesis by enhancing transcription of ATP-Binding cassette transporter A1 gene in a liver X receptorependent manner

Fenofibric acid, the active metabolite of fenofibrate. Increases Apolipoprotein A-I–Mediated High-Density Lipoprotein Biogenesis by enhancing transcription of ATP-Binding cassette transporter A1 gene in a liver X receptor–dependent manner.

ChEBI: A monocarboxylic acid that is 2-methylpropanoic acid substituted by a 4-(4-chlorobenzoyl)phenoxy group at position 2. It is a metabolite of the drug fenofibrate.

General procedure for the synthesis of fenofibric acid from compound (CAS:1159999-13-9): to a solution of compound 104 (5.00 g, 12.2 mmol) in ethanol (150 mL) was added a solution of potassium hydroxide (2.74 g, 48.9 mmol) in ethanol (50 mL). The reaction mixture was heated to reflux and stirred for 16 hours. Upon completion of the reaction, ethanol was removed under vacuum and water (200 mL) was added to the residue. The aqueous solution was washed with ether (2 x 100 mL) to remove nonpolar impurities, followed by acidification of the aqueous solution with 2N HCl to pH 1. The acidified aqueous solution was extracted with ethyl acetate (2 x 150 mL), the organic phases were combined, washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum to give compound 105 (3.57 g, 91% yield) as an off-white solid . The product was characterized by 1H NMR (300 MHz, CD3OD): δ 7.75-7.70 (m, 4H), 7.52 (d, J = 8.6 Hz, 2H), 6.96 (d, J = 9.0 Hz, 2H), 1.65 (s, 6H).

Fenofibric acid is primarily conjugated with glucuronic acid and then excreted in urine. A small amount of fenofibric acid is reduced at the carbonyl moiety to a benzhydrol metabolite, which is, in turn, conjugated with glucuronic acid and excreted in urine. In vitro and in vivo metabolism data indicate that fenofibric acid does not undergo oxidative metabolism (e.g. cytochrome P450) to a significant extent. The enzymes CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4 do not play a role in the metabolism of fenofibric acid.

[1] Patent: WO2009/73138, 2009, A2. Location in patent: Page/Page column 81-82